Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia.
Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

psychiatry

In ancient Greek mythology, the souls of the dead were made to drink from the river Lethe, so that they would forget their past lives. Something analogous happens to genes at the very beginning of life. Right after fertilization, the embryo instructs them to forget what it was like in the egg or sperm where they had come from.

This is part of the “maternal-to-zygote transition”: much of the epigenetic information carried on and around the DNA is wiped clean, so that the embryo can start from a clean slate.

Developmental biologist Lewis Wolpert once said: “It is not birth, marriage or death which is
the most important time in your life, but gastrulation,” referring to when the early embryo separates into layers of cells that eventually make up all the organs. Well, the MZT, which occurs first, comes pretty close in importance.

When this process of epigenetic reprogramming is disrupted, the consequences are often lethal. Emory cell biologists David Katz and Jadiel Wasson discovered that when mouse eggs are missing an enzyme that is critical for the MZT, on the rare instances when the mice survive to adulthood, they display odd repetitive behaviors. Read more

This grant announcement from the American Heart Association caught Lab Land’s eye.Â All three of the scientists involved in this project, examining the connections between hypertension, inflammation and the sympathetic nervous system in PTSD, have Emory connections:

In contrast to evidence that the amygdala stimulates stress responses in adults, researchers at Yerkes National Primate Research Center, Emory University have found that the amygdala has an inhibitory effect on stress hormones during the early development of nonhuman primates.

The amygdala is a region of the brain known to be important for responses to threatening situations and learning about threats. Alterations in the amygdala have been reported in psychiatric disorders such as depression, anxiety disorders like PTSD, schizophrenia and autism spectrum disorder. However, much of what is known about the amygdala comes from research on adults.

â€œOur findings fit into anÂ emerging themeÂ in neuroscience research: that during childhood, there is a switch in amygdala function and connectivity with other brain regions, particularly the prefrontal cortex,â€ says Mar Sanchez, PhD, neuroscience researcher at Yerkes and associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. The first author of the paper is postdoctoral fellow Jessica Raper, PhD.

Some notableÂ links on the amygdala:

*AnÂ effort to correctÂ simplistic views of amygdala as the “fear center” of the brain

*Collection of papers mentioningÂ patient SM, an adult human with an amygdala lesion

This graph, from a recent paper in Nature Neuroscience, describes how variations in the gene FKBP5 make individuals more susceptible to physical and sexual abuse, and thus more likely to develop PTSD (post-traumatic stress disorder).

The paper is the result of a collaboration between Elisabeth Binder and her colleagues at the Max Planck Institute of Psychiatry in Munich, and Emory psychiatrists Kerry Ressler and Bekh Bradley. The population under study is made up of inner-city Atlanta residents, part of the Grady Trauma Project overseen by Ressler and Bradley. This paper analyzes samples from a group of individuals that is more than twice as large as the original 2008 paper defining the effect of FKBP5, and adds mechanistic understanding: how regulation of the FKBP5 gene is perturbed.

Back to the graph — in addition to the effects of the different forms of the gene, it is striking how high the rate of PTSD is for both individuals with the protective and risk forms of FKBP5. Also, for individuals who did not experience abuse, the PTSD rate is actually higher for the â€œprotectiveâ€ form of the gene. On this point, the authors write:

It is, however, possible that the described polymorphisms Gafas Ray Ban outlet define not only risk versus resilience, but possibly environmentally reactive versus less reactive individuals. This would imply that the so-called risk-allele carriers may also profit more from positive environmental change.

The FKBP5 gene encodes a protein that regulates responses to the stress hormone cortisol. Thus, it acts in blood and immune system cells, not only the brain, and is involved in terminating the stress response after the end of a threat. In the paper’s discussion, the authors propose that FKBP5 may have a role in sensitivity to other immune and metabolic diseases, in addition to PTSD and depression.

How can we study depression and antidepressants in animals? They canâ€™t talk and tell us how theyâ€™re feeling. Previously, researchers have used the model of â€œbehavioral despair,â€ with examples of the forced swimming test or the tail suspension test.

Shannon Gourley, PhD

Several psychiatrists have been arguing that a new framework is needed, which better simulates aspects of depression in humans, such as the variety of behavioral changes and the several week time period needed for antidepressants to function. This new framework could help illuminate how depression develops, and lead to new antidepressants that are effective for more people.

Shannon Gourley, who recently joined the Emory-Childrenâ€™s Pediatric Research Center has been taking the approach of examining the lack of motivation and self-defeating behavior that are integral parts of depression.

The Pediatric Research Center is an effort led by Emory University and Childrenâ€™s Healthcare of Atlanta, including partnerships with the Georgia Institute of Technology and Morehouse School of Medicine.

Note: Gretchen Neigh in psychiatry/physiology has been doing work with a similar theme, looking at the effects of adolescent social stress in animal models.

Gourley, neuroscience graduate student Andrew Swanson and their colleagues at Yale, where Gourley was a postdoc with Jane Taylor and Tony Koleske, have a new paper in PNAS on this topic. In particular, they dissect how chronic stress â€“ or exposure to the stress hormone corticosterone â€“ can produce loss of motivation and impaired decision making.

First, the researchers found that exposing rodents to cheap oakleys corticosterone shut off a growth factor called BDNF (brain-derived neurotrophic factor) in the frontal cortex, a region of the brain important for planning and goal-directed behavior. BDNF nourishes neurons and helps keep them alive.

To confirm that BDNF was important in this region of the brain, researchers selectively silenced the gene for BDNF only in the frontal cortex. Both mice exposed to stress hormones and the BDNF-altered mice showed reduced motivation to earn food rewards. Mice would ordinarily press a lever dozens of times to get a food pellet, but the BDNF-altered animals would stop trying earlier â€“ the â€œbreak pointâ€ is 2/3 as high.

â€œDepression is a leading cause of unemployment because people are unable to break out of self-defeating behavioral patterns and to muster the motivation to engage with the world. If we can better understand how to treat these symptoms, we can effect better outcomes for individuals suffering from depression,â€ Gourley says. â€œThe BDNF deficiency alone could account for the loss of motivation that individuals with depression suffer.â€

However, she reports her team was surprised that the loss of BDNF could not account for another aspect of depression: cyclical self-defeating behavior. They modeled this by asking whether mice continue to press a lever for a food reward even when the reward is no longer available.

â€œWhen we made the discovery that reduced BDNF could not account for all of the depression symptoms that we study, we took a step back and looked at the stress response system,â€ Gourley says.

Stress hormone exposure impairs the ability of mice to switch away from fruitless behaviors, but loss of BDNF in the frontal cortex does not. Here, the stress response system itself was the culprit. When her team temporarily blocked the ability of mice to shut off their stress response systems using the drug mifepristone, mice had impaired decision-making. However, their motivation to obtain rewards was not altered. When the drug wore off, they returned to normal.

Gourley says the implication is that effective antidepressants need to be able to attack not one, but two physiological systems: they need to increase levels of BDNF, and they need to help the stress system recover so that it can shut itself off better. A classic trycyclic antidepressant, amitriptyline, can do both and was effective in treating both the motivation and decision making parts of depression in animal models.

The use of tricyclic antidepressants is limited because of side effects and overdose potential. In addition, another challenge in treating depression is that current antidepressants only begin to work after several weeks or months of treatment. This is thought to be because it takes several weeks for these drugsâ€”which act only indirectly on BDNFâ€”to restore BDNF levels back to normal.

She and her team also showed that a drug called riluzole, which acts indirectly but rapidly on BDNF systems, has antidepressant effects in the animal models. Riluzole is currently in use to treat ALS, and reportedly has antidepressant effects in humans. Clinical trials with riluzole in the context of depression are underway.

If you hear someone talking about a stress hormone, theyâ€™re probably talking about cortisol. Itâ€™s released by the adrenal glands in stressful situations, whether you have to escape a bear or just give a speech. Cortisol is supposed to prepare the body for â€œfight or flight.â€

Kerry Ressler, MD, PhD

Let’s step back a bit, and look at how the brain triggers cortisol production: through a peptide produced in the brain called CRF (corticotropin-releasing factor). CRF is elevated in several disorders such as depression and PTSD, and is also thought to be involved in drug and alcohol dependency.

Neurons that make CRF are found in locations all over the brain, so studying them can be tricky. Kerry Ressler and his colleagues have developed an intriguing tool for studying CRF. In the places where CRF is produced in a mouseâ€™s brain, they can take out the gene of their choice.

In a new paper in PNAS, postdoc Georgette Gafford and Ressler use this tool in a subtle way. They have mice where a gene for a GABA receptor, one of the main inhibitory receptors (brakes) in the nervous system, is deleted, but only in the CRF neurons. This basically has the effect of turning up the volume on CRF production in several parts of the brain. It appears that modulating GABA receptors is something that normally happens to regulate CRF production, but in this case, a restraint on these stress-sensitive cells has been taken off.

â€œThese mice are normal in many ways – normal locomotor and pain responses and no difference in depressive-like behavior or Pavlovian fear conditioning. However, these mutants have increased anxiety-like behavior,â€ Gafford and Ressler write.

They also have â€œimpaired extinction of conditioned fear,â€ meaning that they have trouble becoming NOT afraid of something, like a buzzing sound, to which they have been sensitized by shocks. This is analogous to PTSD in which patients remain afraid and aren’t able to successfully inhibit their prior fear learning, even after the context is now safe.Â [A 2011 paper goes into more detail on this biological aspect of PTSD in a civilian population.]

â€œThese data indicate that disturbance of this specific population of neurons causes increased anxiety and impaired fear extinction, and helps us to further understand mechanisms of fear- and anxiety-related disorders such as PTSD,” Ressler and Gafford write.

Ressler, associate professor of psychiatry and behavioral sciences, is a Howard Hughes Medical Investigator, with a laboratory at the Yerkes National Primate Research Center. He is also co-director of the Grady Trauma Project.

Tireless advocacy in the last decade by mental health professionals and people who are affected by mental illness has aimed to reduce the stigma of psychiatric disorders. To determine the influence those efforts have had on news media portrayals, Emory researchers studied newspaper articles using the terms â€œschizophreniaâ€ and â€œschizophrenicâ€ in the years 2000 versus 2010.

â€œThe primary goal of journalists is to give fair, accurate and unbiased reports of news events that will be of interest to the public,â€ says study author Arshya Vahabzadeh, MD, resident psychiatrist in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine.

Arshya Vahabzadeh, MD, resident psychiatrist in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine says that people who suffer from a mental illness often internalize negative references, and develop coping mechanisms that become obstacles to treatment.

â€œA secondary goal is to capture the attention of readers and viewers,â€ he says. â€œUnfortunately, stories linked to a mental illness have been shown to strongly attract readersâ€™ attention, and to contribute to unfavorable public conceptions of mental illness.â€

According to the researchers, the decade from 2000 to 2010 was of particular importance to the study because as the new millennium began, attention increasingly focused on public awareness of mental illness, with mental health professionals, advocacy groups and governmental bodies targeting de-stigmatization of psychiatric disorders.

Vahabzadeh and his colleagues examined hundreds of articles that appeared in five major newspapers during a five-month time period during 2000 and 2010, searching for the terms â€œschizophreniaâ€ and â€œschizophrenicâ€.

The researchers found that during that period in 2000, 7,114 articles were published in the five selected newspapers, 247 of which mentioned schizophrenia. During the same period in 2010, 4,397 articles were published, with 151 articles mentioning schizophrenia.

Although a larger percentage of the articles were published in 2000 than in 2010, the percentage of articles mentioning schizophrenia did not differ. Similarly, there was no significant difference in metaphorical usage of the term â€œschizophreniaâ€ â€“ using the term to describe conflicting decisions or illogical actions.

Of particular concern to investigators was that 60 percent of the human-interest stories in both time periods focused on highly emotive reports of violence, dangerousness and criminality. Murders committed by people with schizophrenia accounted for almost half of such articles. The authors did, however, recognize a smaller proportion of articles focusing on crimes and murder committed by people with schizophrenia in 2010 compared to 2000.

Additionally, despite the fact that people with schizophrenia are more prone to be the victims rather than perpetrators of crime, situations in which people with schizophrenia were reported as victims accounted for only 0.5% of the articles reviewed.

â€œPeople who suffer from a mental illness often internalize these negative references, and develop coping mechanisms that become obstacles to treatment,â€ explains Vahabzadeh.

â€œNegative perceptions also may result in problems for those who are successfully treated,â€ he says. â€œPeople with schizophrenia may encounter stigma when they attempt to integrate into society, build relationships, find employment and even housing. It is important for us as mental health professionals to look for opportunities to educate the media on ways to become a positive force to reduce stigma.â€

Nadine Kaslow, PhD, professor and chief psychologist at the Emory University School of Medicine, whose mentorship inspired the study, says “This study provides invaluable information about the persistence of negative and unfounded portrayals of people living with schizophrenia to the public. It is imperative that everyone interacts with people living with mental illness respectfully and with compassion, and that they be welcomed members of our community.”

In the 1999 film The Matrix, the character Neo is offered a choice between a blue pill (to forget) and a red pill (to remember). If only neuroscience was that simple! It may be that neurons need both red and blue, possibly an elaborate dance of molecules, for a fragile memory to lodge itself in the brain.

The research is a follow-up on theirÂ work probing the role of beta-catenin in fear memory formation. We previously described this protein as acting â€œlike a Velcro strapâ€, attaching cellsâ€™ internal skeletons to proteins on their external membranes that help them adhere to other cells. If brain cells need to change shape and form new connections for memories to be consolidated, we can see how this kind of molecule would be important.

Beta-catenin is also central to a signaling circuit that maintains stem cells and prods an embryo to separate into front and back or top and bottom. This circuit is called â€œWntâ€ (the name is a fusion of the fruit fly gene wingless and a cancer-promoting gene discovered in mice, originally called Int-1).

Maguschak and Ressler wanted to assess the role Wnt signals play in learning and memory. The model system was the same as in their previous work: if mice are electrically shocked just after they hear a certain tone, they gradually learn to fear that tone, and they show that fear by freezing.

Kerry Ressler, MD, PhD

Maguschak saw that in the amygdala, a part of the brain important for fear responses, Wnt genes are turned down during the learning process temporarily but then come back on. If the mice only hear the tone or only get the shock, the genesâ€™ activities donâ€™t change significantly.

She then introduced proteins that perturb Wnt signaling directly into the amygdala. Extra Wnt injected before training, while it didnâ€™t stop the mice from learning to fear the tone, made that training less likely to â€œstick.â€ Two days later, the mice that received Wnt didnâ€™t seem to fear the tone as much.

Hereâ€™s the possibly confusing part: a Wnt inhibitor also impaired fear memory consolidation. In effect, both blue and red pills actually interfered with how well memories endured. The authors suggest this is because Wnt signals have to be turned down during fear memory formation but then turned back up so those memories can solidify. The Wnt signals seem to go along with the adhesive interactions of beta-catenin. It looks like beta-cateninâ€™s stickiness also needs to be tuned down and then back up.

The off-then-on-again requirement Maguschak and Ressler observe is reminiscent of results from cell biologist James Zhengâ€™s lab. He and his colleagues saw that the actin cytoskeleton needed to be weakened and then stabilized during long-term potentiation, an enhancement of connections between neurons thought to lie behind learning and memory.

Several laboratories have identified potential drugs that modify beta-catenin/Wnt. These new results suggest that the timing of when and how to use such drugs to enhance memory may critically important to consider, Ressler says.

“To interfere with memory formation after trauma or enhance memory formation in people with dementia, researchers will clearly need to attend to the full complexity of the dynamics of synaptic plasticity and memory,” he says.

The Monarch School Program is dedicated to providing information and resources to families and school systems throughout Georgia for the education of K-12 students with autism / autistic spectrum disorder.

Educators have known for a long time that children with Autism Spectrum Disorder (ASD) can learn a lot by being in a classroom with typical children. Inclusion (educating students within the general education classroom) gives children with special needs the opportunity to learn in a natural environment and the opportunity to learn social skills from interacting with their classmates. In addition, Inclusion can eventually lead to greater acceptance of these children in the community.

Unfortunately, teachers are not always trained how to help children with special needs function in a typical classroom, nor in ways to ensure successful imitation of the positive role models.

â€œTeachers do not necessarily have the specific training required to teach these children yet, too often, the children with ASD are placed in the classroom with the expectation that the teacher, or the student, will learn to adapt,â€ says Sheila Wagner, M.Ed., assistant director of the Emory Autism Center. â€œWithout the training, many times the student faces failure, when success was the goal.â€

In order to provide some guidance to the school system, the Emory Autism Center received a grant from the Childhood Autism Foundation (CADEF) in 1994 to develop a program that would address Inclusive Education for students with ASD.Â With the help of CADEF, the Monarch Program was created. The program implemented a nationally recognized Inclusion Project that has reached hundreds of students with ASD, thousands of teachers through on-site technical assistance and training, and assisted thousands of typical students in learning about the autism spectrum and children with different behaviors and abilities.

â€œThe Monarch Program has grown to provide school systems with a network of support from curriculum training, to teacher and home/school collaboration, to consultations and social skills curriculum,â€ says Wagner, who serves as the Program Manager of the Monarch School-Age Program at Emory.

â€œBecause of the Monarch Inclusion Project, students with ASD are increasingly able to enjoy exposure to typical students, and teachers are offered some guidance in providing a positive classroom experience.â€

Wagner began her experience in the field of autism more than 30 years ago and has published three books on inclusive programming for students with ASD, as well as a brochure on Aspergerâ€™s syndrome, and a chapter in Grandin & Attwoodâ€™s book Aspergers and Girls.

Nadine Kaslow, PhD, Emory psychologist and professor in the Department of Psychiatry and Behavioral Sciences at Emory, has learned a lot about Intimate Partner Violence (IPV) over the last two decades. In the 1990â€™s, Kaslow began the development of a program that was eventually named the â€œNia Project.â€

Nia is a counseling program for abused and suicidal African American women, funded by grants from the Centers for Disease Control and Prevention (CDC) and the National Institute of Mental Health. The name comes from the Kwanzaa term that means “purpose.”

Nia serves countless numbers of abused and suicidal women who come through Atlantaâ€™s Grady Memorial Hospitalâ€™s emergency department each year. The women come in with black eyes, broken bones, and broken spirits, often inflicted by the people who are supposed to love them the most: their husbands, boyfriends and partners.

According to the CDC, Intimate Partner violence resulted in more than 1,500 deaths in the United States in 2005.Â Statistics from the Commission on Domestic Violence show that African American females experienced intimate partner violence at a rate 35 percent higher than that of white females, and about 22 times the rate of women of other races. The number one killer of African American women ages 15 to 34 is homicide at the hands of a current or former intimate partner.